Probing the mutational landscape of the SARS-CoV-2 spike protein via quantum mechanical modeling of crystallographic structures.

ABSTRACT: We employ a recently developed complexity-reduction quantum mechanical (QM-CR) approach, based on complexity reduction of density functional theory calculations, to characterize the interactions of the SARS-CoV-2 spike receptor binding domain (RBD) with ACE2 host receptors and antibodies. QM-CR operates via ab initio identification of individual amino acid residue's contributions to chemical binding and leads to the identification of the impact of point mutations. Here, we especially focus on the E484K mutation of the viral spike protein. We find that spike residue 484 hinders the spike's binding to the human ACE2 receptor (hACE2). In contrast, the same residue is beneficial in binding to the bat receptor Rhinolophus macrotis ACE2 (macACE2). In agreement with empirical evidence, QM-

SUBMITTER: Zaccaria M 

PROVIDER: S-EPMC9802038 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature